CN102846624B - Compound telmisartan hydrochlorothiazide pharmaceutical composition and preparation method thereof - Google Patents
Compound telmisartan hydrochlorothiazide pharmaceutical composition and preparation method thereof Download PDFInfo
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- CN102846624B CN102846624B CN201210354977.4A CN201210354977A CN102846624B CN 102846624 B CN102846624 B CN 102846624B CN 201210354977 A CN201210354977 A CN 201210354977A CN 102846624 B CN102846624 B CN 102846624B
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- telmisartan
- hydrochlorothiazide
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- -1 Compound telmisartan hydrochlorothiazide Chemical class 0.000 title claims abstract description 38
- 238000002360 preparation method Methods 0.000 title claims abstract description 31
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 22
- RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 claims abstract description 58
- 239000005537 C09CA07 - Telmisartan Substances 0.000 claims abstract description 29
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 claims abstract description 29
- 229960005187 telmisartan Drugs 0.000 claims abstract description 29
- 229960002003 hydrochlorothiazide Drugs 0.000 claims abstract description 28
- 239000000203 mixture Substances 0.000 claims abstract description 27
- OZCVMXDGSSXWFT-UHFFFAOYSA-N 6-chloro-1,1-dioxo-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide;2-[4-[[4-methyl-6-(1-methylbenzimidazol-2-yl)-2-propylbenzimidazol-1-yl]methyl]phenyl]benzoic acid Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O.CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O OZCVMXDGSSXWFT-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000008187 granular material Substances 0.000 claims description 33
- 239000011248 coating agent Substances 0.000 claims description 31
- 238000000576 coating method Methods 0.000 claims description 31
- 229930006000 Sucrose Natural products 0.000 claims description 15
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 15
- 239000000194 fatty acid Substances 0.000 claims description 15
- 229930195729 fatty acid Natural products 0.000 claims description 15
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 15
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 15
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 claims description 15
- 239000005720 sucrose Substances 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 13
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 13
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 13
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 13
- 239000000243 solution Substances 0.000 claims description 11
- 238000010790 dilution Methods 0.000 claims description 10
- 239000012895 dilution Substances 0.000 claims description 10
- 239000012530 fluid Substances 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- 229920000881 Modified starch Polymers 0.000 claims description 5
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 5
- 238000007908 dry granulation Methods 0.000 claims description 5
- 229940093429 polyethylene glycol 6000 Drugs 0.000 claims description 5
- 239000007779 soft material Substances 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- 239000003814 drug Substances 0.000 abstract description 11
- 230000000694 effects Effects 0.000 abstract description 9
- 229940079593 drug Drugs 0.000 abstract description 7
- 238000013270 controlled release Methods 0.000 abstract description 5
- 239000008280 blood Substances 0.000 abstract description 3
- 210000004369 blood Anatomy 0.000 abstract description 3
- 230000007774 longterm Effects 0.000 abstract description 3
- 230000036772 blood pressure Effects 0.000 abstract description 2
- 206010067484 Adverse reaction Diseases 0.000 abstract 1
- 230000006838 adverse reaction Effects 0.000 abstract 1
- 239000010410 layer Substances 0.000 description 27
- 238000012360 testing method Methods 0.000 description 17
- 238000005516 engineering process Methods 0.000 description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- 239000000047 product Substances 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 4
- 238000011835 investigation Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 3
- 229920003081 Povidone K 30 Polymers 0.000 description 3
- 230000003276 anti-hypertensive effect Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000007599 discharging Methods 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 238000005063 solubilization Methods 0.000 description 3
- 230000007928 solubilization Effects 0.000 description 3
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 238000007922 dissolution test Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 238000005286 illumination Methods 0.000 description 2
- 229960003194 meglumine Drugs 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000013112 stability test Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 102000008873 Angiotensin II receptor Human genes 0.000 description 1
- 108050000824 Angiotensin II receptor Proteins 0.000 description 1
- 206010013710 Drug interaction Diseases 0.000 description 1
- 208000007530 Essential hypertension Diseases 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229940077927 altace Drugs 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
- 229940126317 angiotensin II receptor antagonist Drugs 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000035619 diuresis Effects 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 230000008406 drug-drug interaction Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229940082195 hydrochlorothiazide 12.5 mg Drugs 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 229960003401 ramipril Drugs 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 239000007962 solid dispersion Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 229940101538 telmisartan 80 mg Drugs 0.000 description 1
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a compound telmisartan hydrochlorothiazide pharmaceutical composition, which is a tablet. For the tablet, hydrochlorothiazide and telmisartan are prepared into a coated tablet so as to make the telmisartan and the hydrochlorothiazide in the telmisartan hydrochlorothiazide pharmaceutical composition respectively released. The composition has a controlled release effect and improves the bioavailability. The employment of a coated tablet preparation process can make the two medicines effectively released successively. The pharmaceutical composition has a controlled release effect, maintains a long-term blood concentration, has a more stable blood pressure reduction effect, and reduces adverse reactions.
Description
Technical field
The present invention relates to technical field of medicine, relate in particular to telmisartan hydrochlorothiazide pharmaceutical composition and new preparation method thereof.
Background technology
Telmisartan is a kind of novel Altace Ramipril, is a species specificity angiotensin-ii-receptor (AT I type) antagonist.Telmisartan is compared following characteristics with other class antihypertensive drug: have the specificity of receptor acting, antihypertensive function is remarkable, has good diuresis, can improve myocardium narrow obstacle, drug safety, toleration 1 time on the good 1st, taking convenience.
Chemical name is: 4-{[2-n-pro-pyl-4-methyl-6-(1-tolimidazole-2-yl) benzimidazole-1-yl] methyl } xenyl-2-carboxylic acid
Molecular formula: C
33h
30n
4o
2;
Molecular weight: 514.62;
Hydrochlorothiazide
Chemical name is: 3-ethyl-5-methyl-2-(2-ammonia ethoxymethyl)-4-(2-chlorphenyl)-Isosorbide-5-Nitrae-dihydro-6-methyl-3,5-pyridine dicarboxylate salt
Molecular formula: C
20h
25n
2o
5clC
6h
6o
3s;
Molecular weight: 567.1;
Indication: be used for the treatment of essential hypertension.This product fixed dosage compound preparation is used for the treatment of the patient that those alone telmisartans can not fully be controlled blood pressure.
Application number is that the patent of invention of CN02827182.3 discloses a kind of layer tablets, its comprise preparation can be from the dissolubility sheet substrate that contains the telmisartan substantially existing with amorphous form the ground floor of rapid release angiotensin ii receptor antagonist telmisartan, and preparation can be from quickly disintegrating tablet substrate rapid release diuretic as the second layer of hydrochlorothiazide.
The invention that application number is CN201010027255.9 provides a kind of two unit preparations that comprise telmisartan and hydrochlorothiazide, and it comprises the micropill that contains telmisartan, and the solubilization carrier that contains hydrochlorothiazide.Described telmisartan micropill consists of celphere, the medicated layer that contains active component telmisartan and expanding layer.Described hydrochlorothiazide solubilization carrier comprises solubilization carrier material, surfactant-based, the water-soluble cellulose derivative that is selected from polyethylene glycols, polyvidone class, contains polyoxyethylene groups, organic acid and saccharide and alcohols.
Application number be CN201110385329.0 disclosure of the invention a kind of compound tablet that contains telmisartan and hydrochlorothiazide; by telmisartan granule and hydrochlorothiazide granule, mixing rear tabletting makes; wherein by hydrochlorothiazide particle weight; the disintegrating agent that contains 6% ~ 50% weight portion in hydrochlorothiazide granule, and described compound tablet is single-layer sheet.
To telmisartan hydrochlorothiazide, the application in combination of oral medication is studied the inventor, yet beyond thought, because both physicochemical properties of principal agent cause drug interaction, the mutual interference of stripping phase, therefore, such compositions proof can not fully meet effect of drugs.
Owing to being because the dissolution of the hydrochlorothiazide that causes of drug drug interaction is very low, so the method for the conventional raising drug solubility such as similar pulverizing can not play due effect.
Therefore, the object of the invention is to make telmisartan and hydrochlorothiazide in telmisartan hydrochlorothiazide pharmaceutical composition to discharge respectively, this compositions has slow controlled release effect, improves bioavailability.
The inventor studies discovery by lot of experiments, adopts clad sheet preparation technology, can effectively make two medicines successively discharge, and the slow controlled release effect of tool, maintains long-acting blood concentration, and antihypertensive effect is more steady, reduces untoward reaction.
Summary of the invention
The object of the invention is to according to existing adjuvant and working condition, guaranteeing to have lower production cost and simple preparation technology, be suitable under the prerequisite of large-scale industrial production, work out a kind of suitable prescription and form and preparation technology, make telmisartan Esidrix there is good bioavailability and stability of drug products.
For the present invention is clearly described, below first with regard to thinking of the present invention, carry out some explanations.
The first object of the present invention is to provide a kind of Compound Telmisartan hydrochlorothiazide pharmaceutical composition, and this pharmaceutical composition can effectively make two medicines successively discharge, and the slow controlled release effect of tool, maintains long-acting blood concentration, and antihypertensive effect is more steady, reduces untoward reaction.
The second object of the present invention is to provide the preparation method of Compound Telmisartan hydrochlorothiazide pharmaceutical composition of the present invention, the method is simple, prepared pharmaceutical composition, good stability, product yield is high, and cost is low, is easy to realize industrialization, better be applied to clinically, there is more obvious advantage.
For realizing the first object of the present invention, the present invention adopts following technical scheme:
A Compound Telmisartan hydrochlorothiazide pharmaceutical composition, the Compound Telmisartan hydrochlorothiazide pharmaceutical composition described in every 1000, its formula consists of:
Inner layer piece prescription
Outer-skin sheet prescription
Inner layer piece coating fluid prescription
A Compound Telmisartan hydrochlorothiazide pharmaceutical composition, the Compound Telmisartan hydrochlorothiazide pharmaceutical composition described in every 1000, its formula consists of:
Inner layer piece prescription
Outer-skin sheet prescription
Inner layer piece coating fluid prescription
Preparation technology:
1) inner layer piece preparation: hydrochlorothiazide was pulverized after 100 mesh sieves, be placed in positive mixer with microcrystalline Cellulose, polyvinylpolypyrrolidone, pregelatinized Starch, rapid mixing 3-5 minute, add suitable quantity of water, soft material processed, crosses 20 mesh sieves, 50 ± 5 ℃ dry, 20 mesh sieve granulate, add sucrose fatty acid ester, tabletting.
2) inner layer piece coating: take the especially strange L30D-55 of recipe quantity, add isopyknic water dilution the mix homogeneously of the polyethylene glycol 6000 that dissolves recipe quantity; The especially strange NE 30D that takes recipe quantity, adds isopyknic water dilution mix homogeneously, by aforementioned two parts of solution mix homogeneously, adds the Pulvis Talci of recipe quantity, stirs 30 minutes, obtains coating solution.Label is placed in coating bed, keeps bed temperature below 25 ± 5 ℃, carry out coating, after coating completes, at 60 ℃, be dried 24 hours.
3) outer-skin sheet granule preparation: telmisartan was pulverized to 100 mesh sieves; by the sucrose fatty acid ester mix homogeneously of the polyvinylpolypyrrolidone of telmisartan, microcrystalline Cellulose and 2/3 recipe quantity and 1/2 recipe quantity; dry granulation; granulate; again polyvinylpolypyrrolidone and the sucrose fatty acid ester of residue recipe quantity are mixed homogeneously with above-mentioned granule, adopt clad sheet tablet machine to be pressed into clad sheet with hydrochlorothiazide label.
Below by conceptual design and prescription screening explanation the present invention.
By great many of experiments and stability test research, show, due to telmisartan and two principal agents interactions of hydrochlorothiazide, cause just using conventional preparation method, cannot obtain the pharmaceutical preparation that reliable in quality is stable, therefore change thinking, adopt new preparation technology-solid dispersion technology, it is carried out to further Formulation and screening.
Prepared by 1 ordinary tablet of writing out a prescription
| Telmisartan | 80mg |
| Hydrochlorothiazide | 12.5mg |
| Meglumine | 12mg |
| Sodium hydroxide | 4mg |
| Microcrystalline Cellulose | 200mg |
| Crospolyvinylpyrrolidone | 20mg |
| 5% PVP K30 aqueous solution | In right amount |
| Magnesium stearate | 1.4mg |
Detailed production technology:
Telmisartan and each mistake 100 mesh sieves of hydrochlorothiazide is standby.According to recipe quantity, through the double calculating inventory of checking, take respectively telmisartan, hydrochlorothiazide and other adjuvant except magnesium stearate of recipe quantity.Mixed 100 mesh sieves, so that its abundant mix homogeneously.With 5% PVP K30 aqueous solution, as binding agent, with 30 eye mesh screens, granulate, dry the temperature of 55 ± 5 ℃, then use 30 eye mesh screen granulate, add magnesium stearate lubricant to mix, tabletting and get final product.Investigate dissolution test result:
Dissolution determination result
Above result of the test shows: while discharging telmisartan and hydrochlorothiazide, telmisartan has interference to hydrochlorothiazide simultaneously.
Prepared by 2 double-layer tablet of writing out a prescription
Detailed production technology:
Telmisartan and each mistake 100 mesh sieves of hydrochlorothiazide is standby.According to recipe quantity through the double calculating inventory of checking, ground floor granule preparation: the telmisartan, meglumine, the sodium hydroxide that take recipe quantity are dissolved in appropriate 80% alcoholic solution, dissolve completely, add microcrystalline Cellulose and the crospolyvinylpyrrolidone of the recipe quantity of mix homogeneously to granulate, the temperature of 55 ± 5 ℃, be dried and use again 30 eye mesh screen granulate, add magnesium stearate lubricant to mix; Second layer granule preparation: the hydrochlorothiazide, microcrystalline Cellulose, the crospolyvinylpyrrolidone that take respectively recipe quantity mixed 100 mesh sieves, so that its abundant mix homogeneously, with 5% PVP K30 aqueous solution as binding agent, with 30 eye mesh screens, granulate, dry the temperature of 55 ± 5 ℃, use again 30 eye mesh screen granulate, add magnesium stearate lubricant to mix, ground floor granule and second layer granule are placed in to bi-layer tablet press and suppress double-layer tablet and get final product.
Investigate dissolution test result:
Dissolution determination result
Above result of the test shows: while discharging telmisartan and hydrochlorothiazide, telmisartan has interference to hydrochlorothiazide simultaneously.
Prepared by 3 clad sheets of writing out a prescription
1000 tablet recipes
Inner layer piece prescription
Outer-skin sheet prescription
Inner layer piece coating fluid prescription
Preparation technology:
1) inner layer piece preparation: hydrochlorothiazide was pulverized after 100 mesh sieves, be placed in positive mixer with microcrystalline Cellulose, polyvinylpolypyrrolidone, pregelatinized Starch, rapid mixing 3-5 minute, add suitable quantity of water, soft material processed, crosses 20 mesh sieves, 50 ± 5 ℃ dry, 20 mesh sieve granulate, add sucrose fatty acid ester, tabletting.
2) inner layer piece coating: take the especially strange L30D-55 of recipe quantity, add isopyknic water dilution the mix homogeneously of the polyethylene glycol 6000 that dissolves recipe quantity; The especially strange NE 30D that takes recipe quantity, adds isopyknic water dilution mix homogeneously, by aforementioned two parts of solution mix homogeneously, adds the Pulvis Talci of recipe quantity, stirs 30 minutes, obtains coating solution.Label is placed in coating bed, keeps bed temperature below 25 ± 5 ℃, carry out coating, after coating completes, at 60 ℃, be dried 24 hours.
3) outer-skin sheet granule preparation: telmisartan was pulverized to 100 mesh sieves; by the sucrose fatty acid ester mix homogeneously of the polyvinylpolypyrrolidone of telmisartan, microcrystalline Cellulose and 2/3 recipe quantity and 1/2 recipe quantity; dry granulation; granulate; again polyvinylpolypyrrolidone and the sucrose fatty acid ester of residue recipe quantity are mixed homogeneously with above-mentioned granule, adopt clad sheet tablet machine to be pressed into clad sheet with hydrochlorothiazide label.
The clad sheet of preparing according to above prescription and preparation technology discharges respectively two kinds of medicines, and dissolution determination the results are shown in Table:
Above result of the test shows: while discharging telmisartan and hydrochlorothiazide, telmisartan does not interfere with each other hydrochlorothiazide simultaneously.
The inventor adopts the inventive method and most preferred prescription to manufacture experimently three batches of Compound Telmisartan hydrochlorothiazide tablets, and it is carried out to the preliminary investigation of stability.According to the lower requirement of (two appendix XIXC of Chinese Pharmacopoeia version in 2010) " medicine stability guideline " item, influence factor's test, accelerated test, long term test investigation have been carried out respectively, its result shows, Compound Telmisartan hydrochlorothiazide tablet is stable under illumination condition, 60 ℃ of high temperature and relative humidity 75% are investigated 10 days, 40 ℃ of accelerated tests 6 months, deposit 6 months under long term test condition, and each physical and chemical index does not have significant change.
The present invention is through prescription screening, quality research and stability study, result shows that the prescription of telmisartan hydrochlorothiazide of the present invention is reasonable, feasible process, production cost reduces, target level of product quality, through check, can be controlled product quality, product quality draft under condition stable, and bioavailability, infiltration rate, the aspects such as industrialization are all better than prior art, have obtained beyond thought technique effect.
The specific embodiment
Below in conjunction with embodiment, the present invention is described in further detail, but should understands the non-scope that only limits to these embodiment of scope of the present invention.
Embodiment 1
A Compound Telmisartan hydrochlorothiazide pharmaceutical composition, the Compound Telmisartan hydrochlorothiazide pharmaceutical composition described in every 1000, its formula consists of:
Inner layer piece prescription
Outer-skin sheet prescription
Inner layer piece coating fluid prescription
Preparation technology:
1) inner layer piece preparation: hydrochlorothiazide was pulverized after 100 mesh sieves, be placed in positive mixer with microcrystalline Cellulose, polyvinylpolypyrrolidone, pregelatinized Starch, rapid mixing 3-5 minute, add suitable quantity of water, soft material processed, crosses 20 mesh sieves, 50 ± 5 ℃ dry, 20 mesh sieve granulate, add sucrose fatty acid ester, tabletting.
2) inner layer piece coating: take the especially strange L30D-55 of recipe quantity, add isopyknic water dilution the mix homogeneously of the polyethylene glycol 6000 that dissolves recipe quantity; The especially strange NE 30D that takes recipe quantity, adds isopyknic water dilution mix homogeneously, by aforementioned two parts of solution mix homogeneously, adds the Pulvis Talci of recipe quantity, stirs 30 minutes, obtains coating solution.Label is placed in coating bed, keeps bed temperature below 25 ± 5 ℃, carry out coating, after coating completes, at 60 ℃, be dried 24 hours.
3) outer-skin sheet granule preparation: telmisartan was pulverized to 100 mesh sieves; by the sucrose fatty acid ester mix homogeneously of the polyvinylpolypyrrolidone of telmisartan, microcrystalline Cellulose and 2/3 recipe quantity and 1/2 recipe quantity; dry granulation; granulate; again polyvinylpolypyrrolidone and the sucrose fatty acid ester of residue recipe quantity are mixed homogeneously with above-mentioned granule, adopt clad sheet tablet machine to be pressed into clad sheet with hydrochlorothiazide label.
Embodiment 2
A Compound Telmisartan hydrochlorothiazide pharmaceutical composition, the Compound Telmisartan hydrochlorothiazide medicine group described in every 1000
Compound, its formula consists of:
Inner layer piece prescription
Outer-skin sheet prescription
Inner layer piece coating fluid prescription
Preparation technology:
1) inner layer piece preparation: hydrochlorothiazide was pulverized after 100 mesh sieves, be placed in positive mixer with microcrystalline Cellulose, polyvinylpolypyrrolidone, pregelatinized Starch, rapid mixing 3-5 minute, add suitable quantity of water, soft material processed, crosses 20 mesh sieves, 50 ± 5 ℃ dry, 20 mesh sieve granulate, add sucrose fatty acid ester, tabletting.
2) inner layer piece coating: take the especially strange L30D-55 of recipe quantity, add isopyknic water dilution the mix homogeneously of the polyethylene glycol 6000 that dissolves recipe quantity; The especially strange NE 30D that takes recipe quantity, adds isopyknic water dilution mix homogeneously, by aforementioned two parts of solution mix homogeneously, adds the Pulvis Talci of recipe quantity, stirs 30 minutes, obtains coating solution.Label is placed in coating bed, keeps bed temperature below 25 ± 5 ℃, carry out coating, after coating completes, at 60 ℃, be dried 24 hours.
3) outer-skin sheet granule preparation: telmisartan was pulverized to 100 mesh sieves; by the sucrose fatty acid ester mix homogeneously of the polyvinylpolypyrrolidone of telmisartan, microcrystalline Cellulose and 2/3 recipe quantity and 1/2 recipe quantity; dry granulation; granulate; again polyvinylpolypyrrolidone and the sucrose fatty acid ester of residue recipe quantity are mixed homogeneously with above-mentioned granule, adopt clad sheet tablet machine to be pressed into clad sheet with hydrochlorothiazide label.
Test example 1
The study on the stability of Compound Telmisartan hydrochlorothiazide tablet of the present invention
According to the < < People's Republic of China (PRC), take two appendix XIXC medicine stability test guidelines of pharmacopeia > > version in 2010, homemade Compound Telmisartan hydrochlorothiazide tablet sample has been carried out to primary stability investigation
Influence factor's result of the test
By test data, shown, this product is comparatively stable under illumination, high temperature, super-humid conditions.
The accelerated test of Compound Telmisartan hydrochlorothiazide pharmaceutical composition
According to the method for the embodiment of the present invention 1, prepare three batches of Compound Telmisartan hydrochlorothiazide pharmaceutical compositions according to commercially available back, at 40 ℃ ± 2 ℃, the condition of RH75% ± 5% is placed 6 months, during this time respectively at sampling in the 1st, 2,3,6 months, according to stability inspection item, detect, and with 0 day data comparison.
1, investigation project
High spot reviews: character, dissolution, related substance and content.
1 batch of accelerated test result
2 batches of accelerated test results
3 batches of accelerated test results
Above conclusion (of pressure testing) can be found out: this product is placed 6 months every detection indexs and compared no significant difference with 0 month under accelerated test condition, and stability amount is good.
Claims (1)
1. a Compound Telmisartan hydrochlorothiazide pharmaceutical composition, is that telmisartan and hydrochlorothiazide are made to clad sheet, by it is characterized in that, described Compound Telmisartan hydrochlorothiazide pharmaceutical composition, every 1000 composed as follows:
Inner layer piece prescription
Outer-skin sheet prescription
Inner layer piece coating fluid prescription
Prepare 1000, comprise the following steps:
1) inner layer piece preparation: hydrochlorothiazide was pulverized after 100 mesh sieves, be placed in positive mixer with microcrystalline Cellulose, polyvinylpolypyrrolidone, pregelatinized Starch, rapid mixing 3-5 minute, add suitable quantity of water, soft material processed, crosses 20 mesh sieves, 50 ± 5 ℃ dry, 20 mesh sieve granulate, add sucrose fatty acid ester, tabletting;
2) inner layer piece coating: take the especially strange L30D-55 of recipe quantity, add isopyknic water dilution the mix homogeneously of the polyethylene glycol 6000 that dissolves recipe quantity; Take the especially strange NE30D of recipe quantity, add isopyknic water dilution mix homogeneously, by aforementioned two parts of solution mix homogeneously, add the Pulvis Talci of recipe quantity, stir 30 minutes, obtain coating solution, label is placed in coating bed, keeps bed temperature below 25 ± 5 ℃, carry out coating, after coating completes, at 60 ℃, be dried 24 hours;
3) outer-skin sheet granule preparation: telmisartan was pulverized to 100 mesh sieves; by the sucrose fatty acid ester mix homogeneously of the polyvinylpolypyrrolidone of telmisartan, microcrystalline Cellulose and 2/3 recipe quantity and 1/2 recipe quantity; dry granulation; granulate; again polyvinylpolypyrrolidone and the sucrose fatty acid ester of residue recipe quantity are mixed homogeneously with above-mentioned granule, adopt clad sheet tablet machine to be pressed into clad sheet with hydrochlorothiazide label.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210354977.4A CN102846624B (en) | 2012-09-21 | 2012-09-21 | Compound telmisartan hydrochlorothiazide pharmaceutical composition and preparation method thereof |
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| CN201210354977.4A CN102846624B (en) | 2012-09-21 | 2012-09-21 | Compound telmisartan hydrochlorothiazide pharmaceutical composition and preparation method thereof |
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| CN107412180B (en) * | 2017-06-17 | 2020-05-26 | 江西医学高等专科学校 | Paliperidone core-coated tablet and preparation method thereof |
| CN108653227A (en) * | 2018-08-09 | 2018-10-16 | 湖北舒邦药业有限公司 | A kind of Telmisartan hydrochlorothiazide tablets and preparation method thereof |
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| EP2377521A1 (en) * | 2010-03-26 | 2011-10-19 | Abdi Ibrahim Ilac Sanayi ve Ticaret Anonim Sirketi | Pharmaceutical formulations of telmisartan and diuretic combination |
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